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Yttrium oxide (Y2O3) nanoparticles have very wide application areas such as biological imaging, photodynamic therapy, the material sciences, in the chemical synthesis of inorganic compounds, additives in plastic, paint, steel, optics, and iron. Potential risks to human health and the environment should be evaluated in a multi-dimensional perspective when developing nanoparticles for those applications. Therefore, in this research, we aimed to investigate changes in gene expression profiles (genes involved in different biological pathways) influenced by commonly Yttrium oxide (Y2O3) nanoparticle in human U87MG glioma and PC3 prostate cancer cell lines in vitro. The study was planned to be carried out in two stages. In the first stage, cell viability and cytotoxicity parameters were studied using 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide and lactate dehydrogenase release assays, respectively, with human U87MG glioma and human PC3 prostate cancer cell cultures. In the second stage, to obtain a clear insight into the molecular events after exposing, we examined the effects of selected Y2O3 nanoparticle on the expression of genes in U87MG and PC3 cell cultures using RT² Profiler PCR Arrays. Y2O3 nanoparticles have IC20 of 0,18 mg/L and 2,903 mg/L in PC3 and U87MG cell lines, respectively. Y2O3 nanoparticle induced up-regulation of 24 and down-regulation of 22 genes in PC3 cells and up-regulation of 53 and down-regulation of 27 genes in U87MG cells. This study of gene expression profiles affected by nanotoxicity provides critical information for the clinical and environmental applications of Y2O3 nanoparticles. [ABSTRACT FROM AUTHOR]